Genetic variation in angiotensin-converting enzyme–related pathways associated with sudden cardiac arrest risk

Background: Reperfusion following ischemia due to sudden cardiac arrest (SCA) is necessary for survival, but results in additional injury to affected tissues. Regulation of apoptosis has been shown to be important in determining the extent of reperfusion injury. Caspases (CASP) are essential enzymes in the apoptotic cascade and we therefore hypothesized that genetic variation in these enzymes might influence cardiac and brain resuscitation after SCA. To test this, we examined three genes (CASP2, CASP3, CASP9) in a population-based study of SCA survival. Methods: Subjects (mean age 67, 80% male, of European descent) were out-of-hospital SCA patients found in ventricular fibrillation (VF) and attended by paramedics in King County, WA (n=1614). To investigate cardiac resuscitation, we compared subjects who survived to hospital admission (n=827) with those who did not (n=787); for brain resuscitation, we compared subjects who survived to hospital discharge (n=448) with those who did not (n=1166). Associations of 19 SNPs were examined using logistic regression comparing each additional copy of the minor allele. Based on a priori hypotheses, models were adjusted for: age; gender; time from 911 call to arrival of emergency medical services; whether the event was witnessed; occurred in public; and whether bystander CPR was administered. We used within-gene permutation tests to adjust p-values for multiple comparisons. Results: Two SNPs in CASP3 were associated with SCA survival. The A allele of rs4647688 (minor allele frequency (MAF) 0.20) was associated with lower rates of survival to hospital admission (OR (95% CI), adjusted p-value: 0.78 (0.65, 0.93), p =0.043). The T allele of rs2705897 (MAF 0.26) was associated with a higher rate of survival to hospital admission (1.27 (1.07, 1.51), p =0.049). These two SNPs are in almost complete linkage equilibrium (r 2 =0.091). No SNPs in CASP3 were significantly associated with survival to hospital discharge, and no SNPs in CASP2 or CASP9 were significantly associated with either outcome. Conclusions: CASP3 variants are associated with SCA survival in this population. Further work is needed to explore the effect of these variants on regulation of apoptosis during reperfusion following VF arrest, and to replicate these findings in other populations.

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Genetic variation of the angiotensin-converting enzyme gene: increased frequency of the insertion allele in Koreans

Clinical Genetics ◽

10.1111/j.1399-0004.1997.tb02411.x ◽

2008 ◽

Vol 51 (1) ◽

pp. 35-38 ◽

Cited By ~ 10

Author(s):

S. H. Hong ◽

B. Y. Kang ◽

W. H. Park ◽

J. Q. Kim ◽

C. C. Lee

Keyword(s):

Genetic Variation ◽

Angiotensin Converting Enzyme ◽

Angiotensin Converting Enzyme Gene ◽

Converting Enzyme ◽

Enzyme Gene ◽

Insertion Allele

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CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors

The Pharmacogenomics Journal ◽

10.1038/tpj.2015.42 ◽

2015 ◽

Vol 16 (3) ◽

pp. 220-230 ◽

Cited By ~ 24

Author(s):

X Wang ◽

G Wang ◽

J Shi ◽

J Aa ◽

R Comas ◽

...

Keyword(s):

Genetic Variation ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitors ◽

Angiotensin Converting Enzyme Inhibitors ◽

Converting Enzyme ◽

Converting Enzyme Inhibitors

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Cardiac arrest and COVID-19: inflammation, angiotensin-converting enzyme 2, and the destabilization of non-significant coronary artery disease—a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytaa475 ◽

2020 ◽

Author(s):

Sébastien Colombier ◽

Thabodhan Mahendiran ◽

Lars Niclauss ◽

Matthias Kirsch

Keyword(s):

Coronary Artery Disease ◽

Cardiac Arrest ◽

Coronary Artery ◽

Angiotensin Converting Enzyme ◽

Disease Patient ◽

Significant Coronary Artery Disease ◽

Cardiac Complications ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Artery Disease

Abstract Background The new β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears to exhibit cardiovascular pathogenicity through use of angiotensin-converting enzyme 2 (ACE2) for cell entry and the development of a major systemic inflammation. Furthermore, cardiovascular comorbidities increase susceptibility to SARS-CoV-2 infection and the development of a severe form of COronaVIrus Disease 2019 (COVID-19). Case summary We describe the case of a COVID-19 patient whose inaugural presentation was a refractory cardiac arrest secondary to the destabilization of known, non-significant coronary artery disease. Patient was supported by venoarterial extracorporeal life support. After 12 h of support, cardiac function remained stable on low vasopressor support but the patient remained in a coma and brainstem death was diagnosed. Discussion Myocardial injury is frequently seen among critically unwell COVID-19 patients and increases the risk of mortality. This case illustrates several potential mechanisms that are thought to drive the cardiac complications seen in COVID-19. We present the potential role of inflammation and ACE2 in the pathophysiology of COVID-19.

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DNA methylation and genetic variation of the angiotensin converting enzyme (ACE) in depression

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2017.11.003 ◽

2018 ◽

Vol 88 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Dilys Lam ◽

Marie-Laure Ancelin ◽

Karen Ritchie ◽

Richard Saffery ◽

Joanne Ryan

Keyword(s):

Dna Methylation ◽

Genetic Variation ◽

Angiotensin Converting Enzyme ◽

Converting Enzyme

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The influence of angiotensin converting enzyme and bradykinin receptor B2 gene variants on voluntary fluid intake and fluid balance in healthy men during moderate-intensity exercise in the heat

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0307 ◽

2015 ◽

Vol 40 (2) ◽

pp. 184-190 ◽

Cited By ~ 1

Author(s):

Adora M.W. Yau ◽

Andrew D. Moss ◽

Lewis John James ◽

William Gilmore ◽

Jason J. Ashworth ◽

...

Keyword(s):

Genetic Variation ◽

Angiotensin Converting Enzyme ◽

Body Mass ◽

Fluid Balance ◽

Fluid Intake ◽

Moderate Intensity ◽

Converting Enzyme ◽

Moderate Intensity Exercise ◽

Healthy Men ◽

Bradykinin Receptor

Angiotensin converting enzyme (ACE) and bradykinin receptor B2 (B2R) genetic variation may affect thirst because of effects on angiotensin II production and bradykinin activity, respectively. To examine this, 45 healthy Caucasian men completed 60 min of cycle exercise at 62% ± 5% peak oxygen uptake in a room heated to 30.5 ± 0.3 °C with ad libitum fluid intake. Blood samples were collected pre-, mid-, and immediately post-cycle. Fluid intake, body mass loss (BML), sweat loss (determined via changes in body mass and fluid intake), and thirst sensation were recorded. All participants were genotyped for the ACE insert fragment (I) and the B2R insert sequence (P). Participants were homozygous for the wild-type allele (WW or MM), heterozygous (WI or MP) or homozygous for the insert (II or PP). No differences between genotype groups were found in mean (±SD) voluntary fluid intake (WW: 613 ± 388, WI: 753 ± 385, II: 862 ± 421 mL, p = 0.31; MM: 599 ± 322, MP: 745 ± 374, PP: 870 ± 459 mL, p = 0.20), percentage BML or any other fluid balance variables for both the ACE and B2R genes, respectively. Mean thirst perception in the B2R PP group, however, was higher (p < 0.05) than both MM and MP at 30, 45, and 60 min. In conclusion, the results of this study suggest that voluntary fluid intake and fluid balance in healthy men performing 60 min of moderate-intensity exercise in the heat are not predominantly influenced by ACE or B2R genetic variation.

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